Lymphocytic alveolitis is a common finding in individuals infected with human immunodeficiency virus (HIV). Prior studies have indicated that most of the alveolar cells are CD8 cytotoxic T lymphocytes (CTL). Since a major CTL function is defense against viral infections, they may be important in killing HIV-infected CD4 T cells and alveolar macrophages (AM). However, this function could lead to CD4 T cell and AM depletion with attendant morbidity secondary to impaired immune responses. It is not known how CD8 CTL accumulate in the lungs of HIV-infected individu- als. CTL may proliferate when they interact with accessory cells (AC) in the presence of important cytokines such as interleukin-2 and interleukin-4. The bulk of these cytokines come from CD4 T cells, also after interaction with AC. Thus, AC have a critical role in regulating expansion of the CD8 CTL population compared to normal AM. Our lab has previously shown that the AC function of AM from HIV-infected patients is enhanced. This could lead to active CTL proliferation in the lung of these individuals. The current proposal is designed to test the hypothesis that CD8 CTL accumulate in the lung of HIV-infected patients with lymphocytic alveolitis through local proliferation. Furthermore, it is proposed that expansion of the CD8 CTL population in the lung plays a crucial role in CD4 T cell depletion in these patients. To test these hypotheses, the AC function of AM from HIV-infected patients in stimulating autologous T cells will be examined. The activation and differentiation state of lung and blood CTL will be examined. The proliferative capacity of CTL in response to IL-2 and IL-4 as well as virally-infected cells will be studied. The ability of lung and blood T cells to secrete IL-2 and IL-4 will be examined. Finally, the capacity of lung CTL to kill virally-infected autologous CD4 T cells and AC will be assessed. The proposed studies will give important insights into potential mechanisms of lymphocytic alveolitis in HIV-infected patients. In addition, they will suggest an important new mechanism by which CD4 T cells are depleted in the lung of HIV-infected patients and thereby contribute to the immunologic defects so prevalent in these individuals.